PLCE1_HUMAN
ID PLCE1_HUMAN Reviewed; 2302 AA.
AC Q9P212; A6NGW0; A6NLA1; A7MBN7; A8K1D7; B9EIJ6; Q1X6H8; Q5VWL4; Q5VWL5;
AC Q9H9X8; Q9HBX6; Q9HC53; Q9UHV3;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 {ECO:0000305};
DE EC=3.1.4.11 {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11022048};
DE AltName: Full=Pancreas-enriched phospholipase C;
DE AltName: Full=Phosphoinositide phospholipase C-epsilon-1;
DE AltName: Full=Phospholipase C-epsilon-1;
DE Short=PLC-epsilon-1;
GN Name=PLCE1 {ECO:0000312|HGNC:HGNC:17175}; Synonyms=KIAA1516, PLCE, PPLC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CATALYTIC
RP ACTIVITY, COFACTOR, INTERACTION WITH HRAS AND RAP1A, SUBCELLULAR LOCATION,
RP ACTIVITY REGULATION, AND VARIANTS ILE-1777 AND ARG-1927.
RC TISSUE=Fetal brain;
RX PubMed=11022048; DOI=10.1074/jbc.m008324200;
RA Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y.,
RA Shibatohge M., Wu D., Satoh T., Kataoka T.;
RT "Regulation of a novel human phospholipase C, PLCepsilon, through membrane
RT targeting by Ras.";
RL J. Biol. Chem. 276:2752-2757(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF HIS-1452.
RC TISSUE=Heart;
RX PubMed=11022047; DOI=10.1074/jbc.m008119200;
RA Lopez I., Mak E.C., Ding J., Hamm H.E., Lomasney J.W.;
RT "A novel bifunctional phospholipase C that is regulated by Galpha 12 and
RT stimulates the Ras/mitogen-activated protein kinase pathway.";
RL J. Biol. Chem. 276:2758-2765(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-1927.
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [4]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-1927.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1098-2302 (ISOFORMS 1/2), AND VARIANTS
RP ILE-1777 AND ARG-1927.
RC TISSUE=Pancreas;
RA Kawasaki H., Chen E.J., Springett G.M., Graybiel A.M., Housman D.E.;
RT "A novel phospholipase C enriched in pancreas.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1383 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1475-2302 (ISOFORMS 1/2).
RC TISSUE=Brain, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2302 (ISOFORMS 1/2).
RC TISSUE=Brain;
RA Buessow K.;
RT "Sequence of cDNA clone MPMGp800D13530.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11395506; DOI=10.1074/jbc.m103530200;
RA Jin T.-G., Satoh T., Liao Y., Song C., Gao X., Kariya K., Hu C.-D.,
RA Kataoka T.;
RT "Role of the CDC25 homology domain of phospholipase Cepsilon in
RT amplification of Rap1-dependent signaling.";
RL J. Biol. Chem. 276:30301-30307(2001).
RN [12]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11715024; DOI=10.1038/ncb1101-1020;
RA Schmidt M., Evellin S., Weernink P.A.O., von Dorp F., Rehmann H.,
RA Lomasney J.W., Jakobs K.H.;
RT "A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP
RT and a Rap GTPase.";
RL Nat. Cell Biol. 3:1020-1024(2001).
RN [13]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11877431; DOI=10.1074/jbc.m112024200;
RA Evellin S., Nolte J., Tysack K., vom Dorp F., Thiel M., Weernink P.A.O.,
RA Jakobs K.H., Webb E.J., Lomasney J.W., Schmidt M.;
RT "Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine
RT receptor mediated by cyclic AMP and the GTPase Rap2B.";
RL J. Biol. Chem. 277:16805-16813(2002).
RN [14]
RP INTERACTION WITH RAP1A; RAP2A AND RAP2B.
RX PubMed=12444546; DOI=10.1038/sj.onc.1206003;
RA Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T.;
RT "Differential roles of Ras and Rap1 in growth factor-dependent activation
RT of phospholipase C epsilon.";
RL Oncogene 21:8105-8113(2002).
RN [15]
RP FUNCTION.
RX PubMed=12721365; DOI=10.1073/pnas.1031494100;
RA Czyzyk J., Brogdon J.L., Badou A., Henegariu O., Preston Hurlburt P.,
RA Flavell R., Bottomly K.;
RT "Activation of CD4 T cells by Raf-independent effectors of Ras.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:6003-6008(2003).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=15157671; DOI=10.1016/j.cellsig.2004.01.009;
RA vom Dorp F., Sari A.Y., Sanders H., Keiper M., Oude Weernink P.A.,
RA Jakobs K.H., Schmidt M.;
RT "Inhibition of phospholipase C-epsilon by Gi-coupled receptors.";
RL Cell. Signal. 16:921-928(2004).
RN [17]
RP INDUCTION.
RX PubMed=16293787; DOI=10.1161/01.res.0000196578.15385.bb;
RA Wang H., Oestreich E.A., Maekawa N., Bullard T.A., Vikstrom K.L.,
RA Dirksen R.T., Kelley G.G., Blaxall B.C., Smrcka A.V.;
RT "Phospholipase C epsilon modulates beta-adrenergic receptor-dependent
RT cardiac contraction and inhibits cardiac hypertrophy.";
RL Circ. Res. 97:1305-1313(2005).
RN [18]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15558028; DOI=10.1038/sj.onc.1208168;
RA Sorli S.C., Bunney T.D., Sugden P.H., Paterson H.F., Katan M.;
RT "Signaling properties and expression in normal and tumor tissues of two
RT phospholipase C epsilon splice variants.";
RL Oncogene 24:90-100(2005).
RN [19]
RP FUNCTION, INTERACTION WITH RRAS, AND ACTIVITY REGULATION.
RX PubMed=16537651; DOI=10.1242/jcs.02835;
RA Ada-Nguema A.S., Xenias H., Sheetz M.P., Keely P.J.;
RT "The small GTPase R-Ras regulates organization of actin and drives membrane
RT protrusions through the activity of PLCepsilon.";
RL J. Cell Sci. 119:1307-1319(2006).
RN [20]
RP SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH AVIL, AND TISSUE
RP SPECIFICITY.
RX PubMed=29058690; DOI=10.1172/jci94138;
RA Rao J., Ashraf S., Tan W., van der Ven A.T., Gee H.Y., Braun D.A.,
RA Feher K., George S.P., Esmaeilniakooshkghazi A., Choi W.I.,
RA Jobst-Schwan T., Schneider R., Schmidt J.M., Widmeier E., Warejko J.K.,
RA Hermle T., Schapiro D., Lovric S., Shril S., Daga A., Nayir A., Shenoy M.,
RA Tse Y., Bald M., Helmchen U., Mir S., Berdeli A., Kari J.A., El Desoky S.,
RA Soliman N.A., Bagga A., Mane S., Jairajpuri M.A., Lifton R.P., Khurana S.,
RA Martins J.C., Hildebrandt F.;
RT "Advillin acts upstream of phospholipase C 1 in steroid-resistant nephrotic
RT syndrome.";
RL J. Clin. Invest. 127:4257-4269(2017).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2131-2246 OF MUTANT LEU-2176 IN
RP COMPLEX WITH HRAS, STRUCTURE BY NMR OF 2006-2114 AND 2131-2246, AND
RP MUTAGENESIS OF GLN-2140; GLN-2148; ARG-2150; LYS-2171 AND TYR-2174.
RX PubMed=16483931; DOI=10.1016/j.molcel.2006.01.008;
RA Bunney T.D., Harris R., Gandarillas N.L., Josephs M.B., Roe S.M.,
RA Sorli S.C., Paterson H.F., Rodrigues-Lima F., Esposito D., Ponting C.P.,
RA Gierschik P., Pearl L.H., Driscoll P.C., Katan M.;
RT "Structural and mechanistic insights into ras association domains of
RT phospholipase C epsilon.";
RL Mol. Cell 21:495-507(2006).
RN [22]
RP VARIANT NPHS3 LEU-1484, FUNCTION, AND INTERACTION WITH IQGAP1.
RX PubMed=17086182; DOI=10.1038/ng1918;
RA Hinkes B., Wiggins R.C., Gbadegesin R., Vlangos C.N., Seelow D.,
RA Nuernberg G., Garg P., Verma R., Chaib H., Hoskins B.E., Ashraf S.,
RA Becker C., Hennies H.C., Goyal M., Wharram B.L., Schachter A.D.,
RA Mudumana S., Drummond I., Kerjaschki D., Waldherr R., Dietrich A.,
RA Ozaltin F., Bakkaloglu A., Cleper R., Basel-Vanagaite L., Pohl M.,
RA Griebel M., Tsygin A.N., Soylu A., Mueller D., Sorli C.S., Bunney T.D.,
RA Katan M., Liu J., Attanasio M., O'toole J.F., Hasselbacher K., Mucha B.,
RA Otto E.A., Airik R., Kispert A., Kelley G.G., Smrcka A.V., Gudermann T.,
RA Holzman L.B., Nuernberg P., Hildebrandt F.;
RT "Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic
RT syndrome variant that may be reversible.";
RL Nat. Genet. 38:1397-1405(2006).
CC -!- FUNCTION: The production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated
CC by activated phosphatidylinositol-specific phospholipase C enzymes.
CC PLCE1 is a bifunctional enzyme which also regulates small GTPases of
CC the Ras superfamily through its Ras guanine-exchange factor (RasGEF)
CC activity. As an effector of heterotrimeric and small G-protein, it may
CC play a role in cell survival, cell growth, actin organization and T-
CC cell activation. In podocytes, is involved in the regulation of
CC lamellipodia formation. Acts downtream of AVIL to allow ARP2/3 complex
CC assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047,
CC ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024,
CC ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365,
CC ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182,
CC ECO:0000269|PubMed:29058690}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-
CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456,
CC ChEBI:CHEBI:203600; EC=3.1.4.11;
CC Evidence={ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11022048};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:11022048};
CC -!- ACTIVITY REGULATION: Activated by the heterotrimeric G-protein subunits
CC GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC,
CC RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and
CC CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by
CC G(i)-coupled GPCRs. {ECO:0000269|PubMed:11022047,
CC ECO:0000269|PubMed:11022048, ECO:0000269|PubMed:11715024,
CC ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:15157671,
CC ECO:0000269|PubMed:16537651}.
CC -!- SUBUNIT: Interacts with RHOA (By similarity). Interacts with GTP-bound
CC HRAS, RAP1A, RAP2A, RAP2B and RRAS (PubMed:11022048, PubMed:12444546,
CC PubMed:16483931, PubMed:16537651). Interacts with AVIL
CC (PubMed:29058690). Interacts with IQGAP1 (PubMed:17086182).
CC {ECO:0000250|UniProtKB:Q99P84, ECO:0000269|PubMed:11022048,
CC ECO:0000269|PubMed:12444546, ECO:0000269|PubMed:16483931,
CC ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182,
CC ECO:0000269|PubMed:29058690}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane. Golgi
CC apparatus membrane. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:29058690}. Note=Recruited to plasma membrane by
CC activated HRAS and RAP2. Recruited to perinuclear membrane by activated
CC RAP1A. Isoform 1 and isoform 2 associates with Golgi membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PLCepsilon1a;
CC IsoId=Q9P212-1; Sequence=Displayed;
CC Name=2; Synonyms=PLCepsilon1b;
CC IsoId=Q9P212-2; Sequence=VSP_021335, VSP_021336;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in podocytes
CC (PubMed:29058690). {ECO:0000269|PubMed:15558028,
CC ECO:0000269|PubMed:29058690}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Broadly expressed and only absent in
CC peripheral blood leukocytes. {ECO:0000269|PubMed:11022048,
CC ECO:0000269|PubMed:15558028}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Specifically expressed in placenta,
CC lung and spleen. {ECO:0000269|PubMed:11022047,
CC ECO:0000269|PubMed:15558028}.
CC -!- INDUCTION: Overexpressed during heart failure.
CC {ECO:0000269|PubMed:16293787}.
CC -!- DOMAIN: The Ras-associating domain 1 is degenerated and may not bind
CC HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound
CC HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell
CC membrane.
CC -!- DOMAIN: The Ras-GEF domain has a GEF activity towards HRAS and RAP1A.
CC Mediates activation of the mitogen-activated protein kinase pathway.
CC -!- DISEASE: Nephrotic syndrome 3 (NPHS3) [MIM:610725]: A form of nephrotic
CC syndrome, a renal disease clinically characterized by severe
CC proteinuria, resulting in complications such as hypoalbuminemia,
CC hyperlipidemia and edema. Kidney biopsies show non-specific histologic
CC changes such as focal segmental glomerulosclerosis and diffuse
CC mesangial proliferation. Some affected individuals have an inherited
CC steroid-resistant form and progress to end-stage renal failure. Most
CC patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy,
CC which is a pathologic entity characterized by mesangial matrix
CC expansion with no mesangial hypercellularity, hypertrophy of the
CC podocytes, vacuolized podocytes, thickened basement membranes, and
CC diminished patency of the capillary lumen.
CC {ECO:0000269|PubMed:17086182}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF22005.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAG17145.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA96040.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF190642; AAG17145.2; ALT_FRAME; mRNA.
DR EMBL; AF170071; AAG28341.1; -; mRNA.
DR EMBL; AB040949; BAA96040.2; ALT_INIT; mRNA.
DR EMBL; AL139118; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139124; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL389885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50042.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW50043.1; -; Genomic_DNA.
DR EMBL; BC140705; AAI40706.1; -; mRNA.
DR EMBL; BC151854; AAI51855.1; -; mRNA.
DR EMBL; AF117948; AAF22005.1; ALT_FRAME; mRNA.
DR EMBL; AK022543; BAB14090.1; ALT_INIT; mRNA.
DR EMBL; AK289852; BAF82541.1; -; mRNA.
DR EMBL; AY995135; AAY45890.1; -; mRNA.
DR CCDS; CCDS41552.1; -. [Q9P212-1]
DR CCDS; CCDS53555.1; -. [Q9P212-2]
DR RefSeq; NP_001159451.1; NM_001165979.2. [Q9P212-2]
DR RefSeq; NP_001275918.1; NM_001288989.1.
DR RefSeq; NP_057425.3; NM_016341.3. [Q9P212-1]
DR PDB; 2BYE; NMR; -; A=2006-2114.
DR PDB; 2BYF; NMR; -; A=2131-2246.
DR PDB; 2C5L; X-ray; 1.90 A; C/D=2131-2246.
DR PDBsum; 2BYE; -.
DR PDBsum; 2BYF; -.
DR PDBsum; 2C5L; -.
DR AlphaFoldDB; Q9P212; -.
DR BMRB; Q9P212; -.
DR SMR; Q9P212; -.
DR BioGRID; 119370; 15.
DR IntAct; Q9P212; 6.
DR STRING; 9606.ENSP00000360431; -.
DR SwissLipids; SLP:000000663; -.
DR GlyGen; Q9P212; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9P212; -.
DR PhosphoSitePlus; Q9P212; -.
DR BioMuta; PLCE1; -.
DR DMDM; 118595723; -.
DR EPD; Q9P212; -.
DR jPOST; Q9P212; -.
DR MassIVE; Q9P212; -.
DR MaxQB; Q9P212; -.
DR PaxDb; Q9P212; -.
DR PeptideAtlas; Q9P212; -.
DR PRIDE; Q9P212; -.
DR ProteomicsDB; 83705; -. [Q9P212-1]
DR ProteomicsDB; 83706; -. [Q9P212-2]
DR Antibodypedia; 2889; 48 antibodies from 15 providers.
DR DNASU; 51196; -.
DR Ensembl; ENST00000371375.2; ENSP00000360426.1; ENSG00000138193.17. [Q9P212-2]
DR Ensembl; ENST00000371380.8; ENSP00000360431.2; ENSG00000138193.17. [Q9P212-1]
DR Ensembl; ENST00000675218.1; ENSP00000501910.1; ENSG00000138193.17. [Q9P212-2]
DR GeneID; 51196; -.
DR KEGG; hsa:51196; -.
DR MANE-Select; ENST00000371380.8; ENSP00000360431.2; NM_016341.4; NP_057425.3.
DR UCSC; uc001kjk.4; human. [Q9P212-1]
DR CTD; 51196; -.
DR DisGeNET; 51196; -.
DR GeneCards; PLCE1; -.
DR HGNC; HGNC:17175; PLCE1.
DR HPA; ENSG00000138193; Low tissue specificity.
DR MalaCards; PLCE1; -.
DR MIM; 608414; gene.
DR MIM; 610725; phenotype.
DR neXtProt; NX_Q9P212; -.
DR OpenTargets; ENSG00000138193; -.
DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome.
DR PharmGKB; PA33391; -.
DR VEuPathDB; HostDB:ENSG00000138193; -.
DR eggNOG; KOG0169; Eukaryota.
DR GeneTree; ENSGT00940000157356; -.
DR HOGENOM; CLU_001158_0_0_1; -.
DR InParanoid; Q9P212; -.
DR OMA; DLYAVPC; -.
DR OrthoDB; 368239at2759; -.
DR PhylomeDB; Q9P212; -.
DR TreeFam; TF314432; -.
DR BioCyc; MetaCyc:HS06473-MON; -.
DR BRENDA; 3.1.4.11; 2681.
DR PathwayCommons; Q9P212; -.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR SignaLink; Q9P212; -.
DR SIGNOR; Q9P212; -.
DR BioGRID-ORCS; 51196; 18 hits in 1075 CRISPR screens.
DR ChiTaRS; PLCE1; human.
DR EvolutionaryTrace; Q9P212; -.
DR GeneWiki; PLCE1; -.
DR GenomeRNAi; 51196; -.
DR Pharos; Q9P212; Tbio.
DR PRO; PR:Q9P212; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9P212; protein.
DR Bgee; ENSG00000138193; Expressed in renal glomerulus and 189 other tissues.
DR ExpressionAtlas; Q9P212; baseline and differential.
DR Genevisible; Q9P212; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0004629; F:phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0006651; P:diacylglycerol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0032835; P:glomerulus development; IMP:HGNC-UCL.
DR GO; GO:0007507; P:heart development; TAS:UniProtKB.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; TAS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:UniProtKB.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045859; P:regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; TAS:UniProtKB.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR028398; PLC-epsilon1.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR015359; PLC_EF-hand-like.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10336; PTHR10336; 2.
DR PANTHER; PTHR10336:SF6; PTHR10336:SF6; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF09279; EF-hand_like; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00617; RasGEF; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR SMART; SM00239; C2; 1.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00147; RasGEF; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51695; SSF51695; 1.
DR SUPFAM; SSF54236; SSF54236; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Cell projection; Cytoplasm; Disease variant; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transducer.
FT CHAIN 1..2302
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase epsilon-1"
FT /id="PRO_0000256238"
FT DOMAIN 531..790
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 1392..1540
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 1730..1846
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 1851..1976
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 2012..2114
FT /note="Ras-associating 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 2135..2238
FT /note="Ras-associating 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT REGION 1053..1192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1567..1591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1683..1743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1686..1764
FT /note="Required for activation by RHOA, RHOB, GNA12, GNA13
FT and G-beta gamma"
FT /evidence="ECO:0000250"
FT REGION 2260..2302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1057..1084
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1088..1125
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1146..1192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1702..1743
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1407
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 1452
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT MOD_RES 1096
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4S1"
FT VAR_SEQ 1..308
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11022047,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_021335"
FT VAR_SEQ 309..402
FT /note="DVEEDAFKSKKERSTLLVRRFCKNDREVKKSVYTGTRAIVRTLPSGHIGLTA
FT WSYIDQKRNGPLLPCGRVMEPPSTVEIRQDGSQRLSEAQWYP -> MVSEGSAAGRDFA
FT GMEEVRQLHVRFCKGIKIWHQAWFLCSLLGREPQEREAGCQLWLCTLSAVLKVGWLFPL
FT SEVPNFTLLKDGCGCWRLKEDQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11022047,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_021336"
FT VARIANT 469
FT /note="S -> T (in dbSNP:rs17508082)"
FT /id="VAR_031843"
FT VARIANT 548
FT /note="R -> L (in dbSNP:rs17417407)"
FT /id="VAR_031844"
FT VARIANT 1484
FT /note="S -> L (in NPHS3; gives rise to focal segmental
FT glomerulosclerosis rather than diffuse mesangial sclerosis;
FT dbSNP:rs121912605)"
FT /evidence="ECO:0000269|PubMed:17086182"
FT /id="VAR_029883"
FT VARIANT 1575
FT /note="R -> P (in dbSNP:rs2274224)"
FT /id="VAR_031845"
FT VARIANT 1777
FT /note="T -> I (in dbSNP:rs3765524)"
FT /evidence="ECO:0000269|PubMed:11022048, ECO:0000269|Ref.8"
FT /id="VAR_031846"
FT VARIANT 1927
FT /note="H -> R (in dbSNP:rs2274223)"
FT /evidence="ECO:0000269|PubMed:10819331,
FT ECO:0000269|PubMed:11022048, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.8"
FT /id="VAR_031847"
FT MUTAGEN 1452
FT /note="H->L: Loss of the phospholipase C enzymatic
FT activity. Still activates HRAS and the MAP kinase pathway."
FT /evidence="ECO:0000269|PubMed:11022047"
FT MUTAGEN 2140
FT /note="Q->E: Increases 2.8-fold the affinity for HRAS."
FT /evidence="ECO:0000269|PubMed:16483931"
FT MUTAGEN 2148
FT /note="Q->E: Decreases 17.5-fold the affinity for HRAS."
FT /evidence="ECO:0000269|PubMed:16483931"
FT MUTAGEN 2148
FT /note="Q->K: Increases 1.4-fold the affinity for HRAS."
FT /evidence="ECO:0000269|PubMed:16483931"
FT MUTAGEN 2150
FT /note="R->L: Abolishes interaction with HRAS."
FT /evidence="ECO:0000269|PubMed:16483931"
FT MUTAGEN 2171
FT /note="K->L: No effect on HRAS-binding."
FT /evidence="ECO:0000269|PubMed:16483931"
FT MUTAGEN 2174
FT /note="Y->L: Reduces HRAS-binding."
FT /evidence="ECO:0000269|PubMed:16483931"
FT CONFLICT 502
FT /note="G -> S (in Ref. 2; AAG28341)"
FT /evidence="ECO:0000305"
FT CONFLICT 703
FT /note="V -> F (in Ref. 2; AAG28341)"
FT /evidence="ECO:0000305"
FT CONFLICT 1133
FT /note="E -> K (in Ref. 2; AAG28341)"
FT /evidence="ECO:0000305"
FT CONFLICT 1229..1230
FT /note="SR -> QA (in Ref. 8; AAF22005)"
FT /evidence="ECO:0000305"
FT CONFLICT 1456
FT /note="L -> P (in Ref. 1; AAG17145)"
FT /evidence="ECO:0000305"
FT CONFLICT 1571
FT /note="N -> D (in Ref. 9; BAB14090)"
FT /evidence="ECO:0000305"
FT CONFLICT 1575
FT /note="R -> Q (in Ref. 2; AAG28341)"
FT /evidence="ECO:0000305"
FT CONFLICT 1672
FT /note="C -> R (in Ref. 1; AAG17145)"
FT /evidence="ECO:0000305"
FT CONFLICT 1705
FT /note="P -> L (in Ref. 9; BAB14090)"
FT /evidence="ECO:0000305"
FT CONFLICT 2125
FT /note="D -> G (in Ref. 9; BAB14090)"
FT /evidence="ECO:0000305"
FT STRAND 2015..2020
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2022..2031
FT /evidence="ECO:0007829|PDB:2BYE"
FT HELIX 2038..2046
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2049..2052
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2058..2064
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2069..2072
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2081..2084
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2086..2088
FT /evidence="ECO:0007829|PDB:2BYE"
FT HELIX 2090..2096
FT /evidence="ECO:0007829|PDB:2BYE"
FT TURN 2099..2103
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2107..2112
FT /evidence="ECO:0007829|PDB:2BYE"
FT STRAND 2136..2143
FT /evidence="ECO:0007829|PDB:2C5L"
FT STRAND 2150..2156
FT /evidence="ECO:0007829|PDB:2C5L"
FT HELIX 2161..2171
FT /evidence="ECO:0007829|PDB:2C5L"
FT TURN 2172..2174
FT /evidence="ECO:0007829|PDB:2C5L"
FT HELIX 2176..2180
FT /evidence="ECO:0007829|PDB:2C5L"
FT HELIX 2184..2186
FT /evidence="ECO:0007829|PDB:2C5L"
FT STRAND 2187..2194
FT /evidence="ECO:0007829|PDB:2C5L"
FT STRAND 2198..2204
FT /evidence="ECO:0007829|PDB:2BYF"
FT STRAND 2207..2211
FT /evidence="ECO:0007829|PDB:2C5L"
FT HELIX 2218..2223
FT /evidence="ECO:0007829|PDB:2C5L"
FT STRAND 2229..2235
FT /evidence="ECO:0007829|PDB:2C5L"
FT TURN 2236..2238
FT /evidence="ECO:0007829|PDB:2C5L"
FT CONFLICT Q9P212-2:69
FT /note="L -> P (in Ref. 2; AAG28341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2302 AA; 258715 MW; 71DDE446277077A3 CRC64;
MTSEEMTASV LIPVTQRKVV SAQSAADESS EKVSDINISK AHTVRRSGET SHTISQLNKL
KEEPSGSNLP KILSIAREKI VSDENSNEKC WEKIMPDSAK NLNINCNNIL RNHQHGLPQR
QFYEMYNSVA EEDLCLETGI PSPLERKVFP GIQLELDRPS MGISPLGNQS VIIETGRAHP
DSRRAVFHFH YEVDRRMSDT FCTLSENLIL DDCGNCVPLP GGEEKQKKNY VAYTCKLMEL
AKNCDNKNEQ LQCDHCDTLN DKYFCFEGSC EKVDMVYSGD SFCRKDFTDS QAAKTFLSHF
EDFPDNCDDV EEDAFKSKKE RSTLLVRRFC KNDREVKKSV YTGTRAIVRT LPSGHIGLTA
WSYIDQKRNG PLLPCGRVME PPSTVEIRQD GSQRLSEAQW YPIYNAVRRE ETENTVGSLL
HFLTKLPASE TAHGRISVGP CLKQCVRDTV CEYRATLQRT SISQYITGSL LEATTSLGAR
SGLLSTFGGS TGRMMLKERQ PGPSVANSNA LPSSSAGISK ELIDLQPLIQ FPEEVASILM
EQEQTIYRRV LPVDYLCFLT RDLGTPECQS SLPCLKASIS ASILTTQNGE HNALEDLVMR
FNEVSSWVTW LILTAGSMEE KREVFSYLVH VAKCCWNMGN YNAVMEFLAG LRSRKVLKMW
QFMDQSDIET MRSLKDAMAQ HESSCEYRKV VTRALHIPGC KVVPFCGVFL KELCEVLDGA
SGLMKLCPRY NSQEETLEFV ADYSGQDNFL QRVGQNGLKN SEKESTVNSI FQVIRSCNRS
LETDEEDSPS EGNSSRKSSL KDKSRWQFII GDLLDSDNDI FEQSKEYDSH GSEDSQKAFD
HGTELIPWYV LSIQADVHQF LLQGATVIHY DQDTHLSARC FLQLQPDNST LTWVKPTTAS
PASSKAKLGV LNNTAEPGKF PLLGNAGLSS LTEGVLDLFA VKAVYMGHPG IDIHTVCVQN
KLGSMFLSET GVTLLYGLQT TDNRLLHFVA PKHTAKMLFS GLLELTRAVR KMRKFPDQRQ
QWLRKQYVSL YQEDGRYEGP TLAHAVELFG GRRWSARNPS PGTSAKNAEK PNMQRNNTLG
ISTTKKKKKI LMRGESGEVT DDEMATRKAK MHKECRSRSG SDPQDINEQE ESEVNAIANP
PNPLPSRRAH SLTTAGSPNL AAGTSSPIRP VSSPVLSSSN KSPSSAWSSS SWHGRIKGGM
KGFQSFMVSD SNMSFVEFVE LFKSFSVRSR KDLKDLFDVY AVPCNRSGSE SAPLYTNLTI
DENTSDLQPD LDLLTRNVSD LGLFIKSKQQ LSDNQRQISD AIAAASIVTN GTGIESTSLG
IFGVGILQLN DFLVNCQGEH CTYDEILSII QKFEPSISMC HQGLMSFEGF ARFLMDKENF
ASKNDESQEN IKELQLPLSY YYIESSHNTY LTGHQLKGES SVELYSQVLL QGCRSVELDC
WDGDDGMPII YHGHTLTTKI PFKEVVEAID RSAFINSDLP IIISIENHCS LPQQRKMAEI
FKTVFGEKLV TKFLFETDFS DDPMLPSPDQ LRKKVLLKNK KLKAHQTPVD ILKQKAHQLA
SMQVQAYNGG NANPRPANNE EEEDEEDEYD YDYESLSDDN ILEDRPENKS CNDKLQFEYN
EEIPKRIKKA DNSACNKGKV YDMELGEEFY LDQNKKESRQ IAPELSDLVI YCQAVKFPGL
STLNASGSSR GKERKSRKSI FGNNPGRMSP GETASFNKTS GKSSCEGIRQ TWEESSSPLN
PTTSLSAIIR TPKCYHISSL NENAAKRLCR RYSQKLTQHT ACQLLRTYPA ATRIDSSNPN
PLMFWLHGIQ LVALNYQTDD LPLHLNAAMF EANGGCGYVL KPPVLWDKNC PMYQKFSPLE
RDLDSMDPAV YSLTIVSGQN VCPSNSMGSP CIEVDVLGMP LDSCHFRTKP IHRNTLNPMW
NEQFLFHVHF EDLVFLRFAV VENNSSAVTA QRIIPLKALK RGYRHLQLRN LHNEVLEISS
LFINSRRMEE NSSGNTMSAS SMFNTEERKC LQTHRVTVHG VPGPEPFTVF TINGGTKAKQ
LLQQILTNEQ DIKPVTTDYF LMEEKYFISK EKNECRKQPF QRAIGPEEEI MQILSSWFPE
EGYMGRIVLK TQQENLEEKN IVQDDKEVIL SSEEESFFVQ VHDVSPEQPR TVIKAPRVST
AQDVIQQTLC KAKYSYSILS NPNPSDYVLL EEVVKDTTNK KTTTPKSSQR VLLDQECVFQ
AQSKWKGAGK FILKLKEQVQ ASREDKKKGI SFASELKKLT KSTKQPRGLT SPSQLLTSES
IQTKEEKPVG GLSSSDTMDY RQ
